Is FDFT1 p.Ser355Phe (c.1064C>T) pathogenic?

FDFT1 p.Ser355Phe (c.1064C>T) is classified Uncertain significance in FDFT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.1587); Very rare (popmax 0.00223%, eas).

How common is FDFT1 p.Ser355Phe (c.1064C>T) in the general population?

FDFT1 p.Ser355Phe (c.1064C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about FDFT1 p.Ser355Phe (c.1064C>T)?

AlphaMissense predicts likely benign (score 0.1587) — an in-silico prediction, not a clinical call.

FDFT1 p.Ser355Phe

c.1064C>T · VCV3514554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1587 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1587	likely benign
REVEL	0.397	indeterminate
SaProt	LLR -7.74	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -1.6, phastCons 0.99
Regional constraint	o/e 1.77	unconstrained · MANE · 36 kb · p 1.6e-69 · regional, not allelic
Overall
CADD	19.25	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000558% 9/1,613,130 alleles · very rare exomes 8/1,460,920 · genomes 1/152,210 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
South Asian	0.0011%	90,882
European (non-Finnish)	0.000593%	168,525

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FDFT1
Protein: p.Ser355Phe
Coding: c.1064C>T
MANE Select: NM_004462
Type: single nucleotide variant
Location: chr8:11838419 (GRCh38)
Gene constraint: LOEUF 1.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.14 · 32 PDB

Full FDFT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FDFT1 c.100-85G>C Uncertain significance ★★ same type
FDFT1 p.Ala333Ser Uncertain significance ★★ ⚠ same type
FDFT1 p.Asn265Ser Uncertain significance ★★ ⚠ same type
FDFT1 p.Gly151Asp Uncertain significance ★★ ⚠ same type
FDFT1 p.Ile252Thr Uncertain significance ★★ ⚠ same type
FDFT1 p.Phe210Leu Uncertain significance ★★ ⚠ same type
FDFT1 p.Ser102Cys Uncertain significance ★★ ⚠ same type
FDFT1 c.100-179C>G Likely benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/fdft1-p-ser355phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown